Nodal-dependent Cripto signaling promotes cardiomyogenesis and redirects the neural fate of embryonic stem cells

The molecular mechanisms controlling inductive events leading to the specification and terminal differentiation of cardiomyocytes are still largely unknown. We have investigated the role of Cripto, an EGF-CFC factor, in the earliest stages of cardiomyogenesis. We find that both the timing of initiation and the duration of Cripto signaling are crucial for priming differentiation of embryonic stem (ES) cells into cardiomyocytes, indicating that Cripto acts early to determine the cardiac fate. Furthermore, we show that failure to activate Cripto signaling in this early window of time results in a direct conversion of ES cells into a neural fate. Moreover, the induction of Cripto activates the Smad2 pathway, and overexpression of activated forms of type I receptor ActRIB compensates for the lack of Cripto signaling in promoting cardiomyogenesis. Finally, we show that Nodal antagonists inhibit Cripto-regulated cardiomyocyte induction and differentiation in ES cells. All together our findings provide evidence for a novel role of the Nodal/Cripto/Alk4 pathway in this process

Vinculin Controls PTEN Protein Level by Maintaining the Interaction of the Adherens Junction Protein β-Catenin with the Scaffolding Protein MAGI-2

PTEN is a frequently mutated tumor suppressor in malignancies. Interestingly, some malignancies exhibit undetectable PTEN protein without mutations or loss of PTEN mRNA. The cause(s) for this reduction in PTEN is unknown. Cancer cells frequently exhibit loss of cadherin, beta-catenin, alpha-catenin and/or vinculin, key elements of adherens junctions. Here we show that F9 vinculin-null (vin(-/-)) cells lack PTEN protein despite normal PTEN mRNA levels. Their PTEN protein expression was restored by transfection with vinculin or by inhibition of PTEN degradation. F9 vin(-/-) cells express PTEN protein upon transfection with a vinculin fragment (amino acids 243-1066) that is capable of interacting with alpha-catenin but unable to target into focal adhesions. On the other hand, disruption of adherens junctions with an E-cadherin blocking antibody reduced PTEN protein to undetectable levels in wild-type F9 cells. PTEN protein levels were restored in F9 vin(-/-) cells upon transfection with an E-cadherin-alpha-catenin fusion protein, which targets into adherens junctions and interacts with beta-catenin in F9 vin(-/-) cells. beta-Catenin is known to interact with MAGI-2. MAGI-2 interaction with PTEN in the cell membrane is known to prevent PTEN protein degradation. Thus, MAGI-2 overexpression in F9 vin(-/-) cells restored PTEN protein levels. Moreover, expression of vinculin mutants that reinstated the disrupted interactions of beta-catenin with MAGI-2 in F9 vin(-/-) cells also restored PTEN protein levels. These studies indicate that PTEN protein levels are dependent on the maintenance of beta-catenin-MAGI-2 interaction, in which vinculin plays a critical role

Non-Pharmacological interventions designed to reduce health risks due to unhealthy eating behaviour and linked risky or excessive drinking in adults aged 18-25 years:A systematic review protocol

BACKGROUND: Excess body weight and heavy alcohol consumption are two of the greatest contributors to global disease. Alcohol use peaks in early adulthood. Alcohol consumption can also exacerbate weight gain. A high body mass index and heavy drinking are independently associated with liver disease but, in combination, they produce an intensified risk of damage, with individuals from lower socio-economic status groups disproportionately affected. METHODS: We will conduct searches in MEDLINE, Embase, PubMed, PsycINFO, ERIC, ASSIA, Web of Knowledge (WoK), Scopus, CINAHL via EBSCO, LILACS, CENTRAL and ProQuest Dissertations and Theses for studies that assess targeted preventative interventions of any length of time or duration of follow-up that are focused on reducing unhealthy eating behaviour and linked risky alcohol use in 18-25-year-olds. Primary outcomes will be reported changes in: (1) dietary, nutritional or energy intake and (2) alcohol consumption. We will include all randomised controlled trials (RCTs) including cluster RCTs; randomised trials; non-randomised controlled trials; interrupted time series; quasi-experimental; cohort involving concurrent or historical controls and controlled before and after studies. Database searches will be supplemented with searches of Google Scholar, hand searches of key journals and backward and forward citation searches of reference lists of identified papers. Search records will be independently screened by two researchers, with full-text copies of potentially relevant papers retrieved for in-depth review against the inclusion criteria. Methodological quality of RCTs will be evaluated using the Cochrane risk of bias tool. Other study designs will be evaluated using the Cochrane Public Health Review Group's recommended Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Studies will be pooled by meta-analysis and/or narrative synthesis as appropriate for the nature of the data retrieved. DISCUSSION: It is anticipated that exploration of intervention effectiveness and characteristics (including theory base, behaviour change technique; modality, delivery agent(s) and training of intervention deliverers, including their professional status; and frequency/duration of exposure) will aid subsequent co-design and piloting of a future intervention to help reduce health risk and social inequalities due to excess weight gain and alcohol consumption. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016040128

Examining Associations between Body Mass Index in 18⁻25 Year-Olds and Energy Intake from Alcohol:Findings from the Health Survey for England and the Scottish Health Survey

Evidence on the relationship between alcohol consumption and body mass index (BMI) is mixed, particularly for young adults. This study explored the relationship between energy obtained from alcoholic beverages and BMI using data for 18-25 year-olds (n = 7691) from pooled cross-sections of the 2008⁻2014 Health Survey for England and the Scottish Health Survey. Energy obtained from alcoholic beverages (excluding mixers) on the heaviest drinking day in the past week was expressed as percentage of total recommended dietary allowance (RDA) of energy (% RDA Energy). Linear regressions were estimated of BMI on alcohol intake categories controlling for intake frequency, physical activity, longstanding illness and other covariates, with separate analyses for men and women, and by beverage type. Significant associations with BMI were observed with the 'Very High' category of alcohol intake (>75% RDA Energy) for men (p 50% to 75% RDA Energy) (p 0⁻25% RDA Energy) category. Young adults drinking the highest levels of alcohol on a single occasion were more likely to be obese than those with the lowest intake. Interventions to address internationally rising youth obesity rates should also consider reducing alcohol consumption by increasing alcohol prices, and reducing availability and marketing exposure

Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip

UV stimulation of prostate cells causes an apoptotic response that is dependent on the zinc finger transcription factor Egr1; downstream targets of Egr1 in this response were identified

Non-Pharmacological Interventions to Reduce Unhealthy Eating and Risky Drinking in Young Adults Aged 18–25 Years::A Systematic Review and Meta-Analysis

Alcohol use peaks in early adulthood and can contribute both directly and indirectly to unhealthy weight gain. This review aimed to systematically evaluate the effectiveness of preventative targeted interventions focused on reducing unhealthy eating behavior and linked alcohol use in 18⁻25-year-olds. Twelve electronic databases were searched from inception to June 2018 for trials or experimental studies, of any duration or follow-up. Eight studies (seven with student populations) met the inclusion criteria. Pooled estimates demonstrated inconclusive evidence that receiving an intervention resulted in changes to self-reported fruit and vegetable consumption (mean change/daily servings: 0.33; 95% CI -0.22 to 0.87) and alcohol consumption (mean reduction of 0.6 units/week; CI -1.35 to 0.19). There was also little difference in the number of binge drinking episodes per week between intervention and control groups (-0.01 sessions; CI -0.07 to 0.04). This review identified only a small number of relevant studies. Importantly, included studies did not assess whether (and how) unhealthy eating behaviors and alcohol use link together. Further exploratory work is needed to inform the development of appropriate interventions, with outcome measures that have the capacity to link food and alcohol consumption, in order to establish behavior change in this population group

Online dietary intake estimation : Reproducibility and validity of the Food4Me food frequency questionnaire against a 4-day weighed food record

©Rosalind Fallaize, Hannah Forster, Anna L Macready, Marianne C Walsh, John C Mathers, Lorraine Brennan, Eileen R Gibney, Michael J Gibney, Julie A Lovegrove. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.08.2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.Background: Advances in nutritional assessment are continuing to embrace developments in computer technology. The online Food4Me food frequency questionnaire (FFQ) was created as an electronic system for the collection of nutrient intake data. To ensure its accuracy in assessing both nutrient and food group intake, further validation against data obtained using a reliable, but independent, instrument and assessment of its reproducibility are required. Objective: The aim was to assess the reproducibility and validity of the Food4Me FFQ against a 4-day weighed food record (WFR). Methods: Reproducibility of the Food4Me FFQ was assessed using test-retest methodology by asking participants to complete the FFQ on 2 occasions 4 weeks apart. To assess the validity of the Food4Me FFQ against the 4-day WFR, half the participants were also asked to complete a 4-day WFR 1 week after the first administration of the Food4Me FFQ. Level of agreement between nutrient and food group intakes estimated by the repeated Food4Me FFQ and the Food4Me FFQ and 4-day WFR were evaluated using Bland-Altman methodology and classification into quartiles of daily intake. Crude unadjusted correlation coefficients were also calculated for nutrient and food group intakes. Results: In total, 100 people participated in the assessment of reproducibility (mean age 32, SD 12 years), and 49 of these (mean age 27, SD 8 years) also took part in the assessment of validity. Crude unadjusted correlations for repeated Food4Me FFQ ranged from .65 (vitamin D) to .90 (alcohol). The mean cross-classification into "exact agreement plus adjacent" was 92% for both nutrient and food group intakes, and Bland-Altman plots showed good agreement for energy-adjusted macronutrient intakes. Agreement between the Food4Me FFQ and 4-day WFR varied, with crude unadjusted correlations ranging from .23 (vitamin D) to .65 (protein, % total energy) for nutrient intakes and .11 (soups, sauces and miscellaneous foods) to .73 (yogurts) for food group intake. The mean cross-classification into "exact agreement plus adjacent" was 80% and 78% for nutrient and food group intake, respectively. There were no significant differences between energy intakes estimated using the Food4Me FFQ and 4-day WFR, and Bland-Altman plots showed good agreement for both energy and energy-controlled nutrient intakes. Conclusions: The results demonstrate that the online Food4Me FFQ is reproducible for assessing nutrient and food group intake and has moderate agreement with the 4-day WFR for assessing energy and energy-adjusted nutrient intakes. The Food4Me FFQ is a suitable online tool for assessing dietary intake in healthy adults.Peer reviewedFinal Published versio

Exploring the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults (aged 18–25)::A qualitative research study

Alcohol use peaks in early adulthood and can contribute both directly and indirectly to unhealthy weight gain. This is the first qualitative study to explore the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults. We conducted 45 in-depth interviews with 18–25-year-olds in North-East England to inform development of a dual-focused intervention to reduce health risk due to excess weight gain and alcohol use. Data were analysed thematically, following the principles of constant comparison, resulting in three intersecting themes: (1) how food and alcohol consumption currently link together for this population group; (2) influences upon linked eating and drinking behaviours and (3) young adults’ feelings and concerns about linked eating and drinking behaviours. Socio-cultural, physical and emotional links between food and alcohol consumption were an unquestioned norm among young adults. Eating patterns linked to alcohol use were not tied only to hunger, but also to sociability, traditions and identity. Young adults conceptualised and calculated risks to weight, appearance and social status, rather than to long-term health. This study is the first to evidence the deeply interconnected nature of food and alcohol consumption for many young adults. Findings have important implications for intervention development, UK public health policy and practice, and point to a need for similar research in other countries